Peptide inhibitors of urokinase receptor activity

Abstract

Effective urokinase-type plasminogen activator receptor antagonists have sequences selected from the group AEPMPHSLNFSQYLWYT, AEWHPGLSFGSYLWSKT, AEHTYSSLWDTYSPLAF, AESSLWTRYAWPSMPSY, AELDLWMRHYPLSFSNR, AEWSFYNLIHILPEPQTIF, AETLFMDLWHDKHILLT, AEPLDLWSLYSLPLAM, AESLPTLTSILWGKESV, AESQTGTLNTLFWNTLR, AESSLWRIFSPSALMMS, AEPALLNWSFFFNPGLH, AEAWFLSNTMKALSARL, AEPTLWQLYQFPLRLSG, AEISFSELMWLRSTPAF, AEWITSSPPLTQYLWGF, AEMHRSLWEWYVPNQSA, AEIKTDFXGWLGLWDLYSM, AEILNFPLWHEPLWSTE, AELSEADLWITWFGMGS, AESVQYSKLWKPNTTLA, AEPLSLYQKKTLRHFAN, AELPRTNPVTAVKNPSF, AEQLNRSIPDLQFSMFN, and AESHIKSLLDSSTWFLP, or active analogs or active portions thereof.

What is claimed: 
     
       1. A peptide selected from the group consisting of AEPMPHSLNFSQYLWYT (SEQ ID NO:1),   AEWHPGLSFGSYLWSKT (SEQ ID NO:2),   AEHTYSSLWDTYSPLAF (SEQ ID NO:3),   AESSLWTRYAWPSMPSY (SEQ ID NO:4),   AELDLWMRHYPLSFSNR (SEQ ID NO:5),   AEWSFYNLHLPEPQTIF (SEQ ID NO:6),   AEPLDLWSLYSLPPLAM (SEQ ID NO:8),   AEPALLNWSFFFNPGLH (SEQ ID NO: 12),   AEAWELSNTMKALSARL (SEQ ID NO:13),   AEPTLWQLYQFPLRLSG (SEQ ID NO:14), active analogs and active portions of said peptides.     
     
     
       2. A protein comprising a sequence selected from the group consisting of AEPMPHSLNFSQYLWYT (SEQ ID NO:1),   AEWHPGLSFGSYLWSKT (SEQ ID NO:2),   AEHTYSSLWDTYSPLAF (SEQ ID NO:3),   AESSLWTRYAWPSMPSY (SEQ ID NO:4),   AELDLWMRHYPLSFSNR (SEQ ID NO:5),   AEWSFYNLHLPEPQTIF (SEQ ID NO:6),   AEPLDLWSLYSLPPLAM (SEQ ID NO:8),   AEPALLNWSFFFNPGLH (SEQ ID NO:12),   AEAWFLSNTMKALSARL (SEQ ID NO:13),   AEPTLWQLYQFPLRLSG (SEQ ID NO:14), active analog and active portions of said peptides.     
     
     
       3. A composition useful for treating disorders mediated by human urokinase plasminogen activator receptor (huPAR), said composition comprising: a pharmaceutically acceptable excipient, and an effective amount of a peptide selected from the group consisting of   AEPMPHSLNFSQYLWYT (SEQ ID NO:1),   AEWHPGLSFGSYLWSKT (SEQ ID NO:2),   AEHTYSSLWDTYSPLAF (SEQ ID NO:3),   AESSLWTRYAWPSMPSY (SEQ ID NO:4),   AELDLWMRHYPLSFSNR (SEQ ID NO:5),   AEWSFYNLHIPEPQTIF (SEQ ID NO:6),   AEPLDLWSLYSLPPLAM (SEQ ID NO:8),   AEPALLNWSFFFNPGLH (SEQ ID NO:12),   AEAWFLSNTMKALSARL (SEQ ID NO:13),   AEPTLWQLYQFPLRLSG (SEQ ID NO:14), active analogs and active portions of said peptides.       
     
     
       4. The composition of claim 3, wherein said huPAR-mediated disorder is selected from the group consisting of metastasis, inappropriate angiogenesis, and chronic inflammation. 
     
     
       5. The composition of claim 3, wherein said huPAR-mediated disorder is selected from the group consisting of Kaposi's sarcoma, diabetic retinopathy, and rheumatoid arthritis. 
     
     
       6. The composition of claim 3, wherein said composition is administered by instillation in the eye. 
     
     
       7. A method for treating disorders mediated by human urokinase plasminogen activator receptor (huPAR), said method comprising: administering an effective amount of a peptide selected from the group consisting of: AEPMPHSLNFSQYLWYT (SEQ ID NO:1),   AEWHPGLSFGSYLWSKT (SEQ ID NO:2),   AEHTYSSLWDTYSPLAF (SEQ ID NO:3),   AESSLWTRYAWPSMPSY (SEQ ID NO:4),   AELDLWMRHYPLSFSNR (SEQ ID NO:5),   AEWSFYNLHLPEPQTIF (SEQ ID NO:6),   AEPLDLWSLYSLPPLAM (SEQ ID NO:8),   AEPALLNWSFFFNPGLH (SEQ ID NO:12),   AEAWFLSNTMKALSARL (SEQ ID NO:13),   AEPTLWQLYQFPLRLSG (SEQ ID NO:14), active analogs and active portions of said peptides.       
     
     
       8. The method of claim 7, wherein said huPAR-mediated disorder is selected from the group consisting of metastasis, inappropriate angiogenesis, and chronic inflammation. 
     
     
       9. The method of claim 7, wherein said huPAR-mediated disorder is selected from the group consisting of Kaposi's sarcoma, diabetic retinopathy, and rheumatoid arthritis. 
     
     
       10. The method of claim 7, wherein said composition is administered by instillation in the eye.